Abstract

BACKGROUND: This study used network pharmacology method and cell model to assess the effects of Radix Astragali (RA) on cholangiocarcinoma (CCA) and to predict core targets and molecular mechanisms.

MATERIAL AND METHODS: We performed an in vitro study to assess the effect of RA on CCA using CCK8 assay, the Live-Cell Analysis System, and trypan blue staining. The components and targets of RA were analyzed using the Traditional Chinese Medicine Systems Pharmacology database, and genes associated with CCA were retrieved from the GeneCards and OMIM platforms. Protein–protein interactions were analyzed with the STRING platform. The components–targets–disease network was built by Cytoscape. The TIMER database revealed the expression of core targets with diverse immune infiltration levels. GO and KEGG analyses were performed to identify molecular-biology processes and signaling pathways. The predictions were verified by Western blotting.

RESULTS: Concentration-dependent antitumor activity was confirmed in the cholangiocarcinoma QBC939 cell line treated with RA. RA contained 16 active compounds, with quercetin and kaempferol as the core compounds. The most important biotargets for RA in CCA were caspase 3, MAPK8, MYC, EGFR, and PARP. The TIMER database revealed that the expression of caspase3 and MYC was related with diverse immune infiltration levels of CCA. The results of Western blotting showed RA significantly influenced the expression of the 5 targets that network pharmacology predicted.

CONCLUSIONS: RA is an active medicinal material that can be developed into a safe and effective multi-targeted anticancer treatment for CCA.

Keywords: Cholangiocarcinoma, Pharmacologic Actions, Antineoplastic Agents, Phytogenic, Astragalus propinquus, Bile Duct Neoplasms, Drugs, Chinese Herbal, Treatment Outcome